The evidence is becoming overwhelming that the GABA system disturbances are a critical hallmark of schizophrenia. The data indicate that these processes are present across different brain regions, albeit with some notable differences in the exact genes affected. Synthesizing the observations from the recent scientific reports strongly suggest that the observed GABA system disturbances arise as a result of complex genetic-epigenetic-environmental-adaptational events. While we currently do not understand the nature of these interactions, it is clear that this will become a major focus of translational neuroscience over the next several years, including dissecting the pathophysiology of these events using in vitro and in vivo experimental models.

View all comments by Karoly Mirnics

  I recommend the Primary Papers

The three papers discussed in the above News article are the most recent to imply dysregulation of the cortical GABAergic system in schizophrenia and related disease. Each paper adds a new twist to the story—molecular changes in the hippocampus of schizophrenia and bipolar subjects show striking differences dependent on layer and subregion (Benes et al), and in prefrontal cortex, there is mounting evidence that changes in the "GABA-transcriptome" affect certain subtypes of inhibitory interneurons (Hashimoto et al). The polymorphisms in the GAD1/GAD67 (GABA synthesis) gene which Straub el al. identified as genetic modifiers for cognitive performance and as schizophrenia risk factors will undoubtedly spur further interest in the field; it will be interesting to find out in future studies whether these genetic variants determine the longitudinal course/outcome of the disease, treatment response etc etc.

View all comments by Schahram Akbarian